A Topological Framework for the Computation of the HOMFLY Polynomial and Its Application to Proteins

Polymers can be modeled as open polygonal paths and their closure generates knots. Knotted proteins detection is currently achieved via high-throughput methods based on a common framework insensitive to the handedness of knots. Here we propose a topological framework for the computation of the HOMFLY polynomial, an handedness-sensitive invariant. Our approach couples a multi-component reduction scheme with the polynomial computation. After validation on tabulated knots and links the framework was applied to the entire Protein Data Bank along with a set of selected topological checks that allowed to discard artificially entangled structures. This led to an up-to-date table of knotted proteins that also includes two newly detected right-handed trefoil knots in recently deposited protein structures. The application range of our framework is not limited to proteins and it can be extended to the topological analysis of biological and synthetic polymers and more generally to arbitrary polygonal paths.Comment: 20 pages, 7 figure

Rknots: topological analysis of knotted biopolymers with R

Motivation: Rknots is a flexible R package providing tools for the detection and characterization of topological knots in biological polymers. The package is well documented and provides a simple syntax for data import and preprocessing, structure reduction, topological analyses and 2D and 3D visualization. Remarkably, Rknots is not limited to protein knots and allows researchers from interdisciplinary fields to analyze different topological structures and to develop simple yet fully custom pipelines. Availability: Rknots is distributed under the GPL-2 license and is available from the CRAN (the Comprehensive R Archive network) at http://cran.r-project.org/web/packages/Rknots Contact: [email protected] Supplementary Information: Supplementary data are available at Bioinformatics onlin

Synergistic activity of antifungal drugs and lipopeptide AC7 against Candida albicans biofilm on silicone

The occurrence of Candida albicans device-associated infections is tightly correlated to the ability of this fungus to form biofilms. The presence of this three-dimensional structure protects cells from host defenses, and significantly increases their resistance to antifungal agents. Lipopeptide biosurfactants are microbial products with interesting antibacterial, antifungal and anti-adhesive properties. Aim of the present study was to investigate a possible synergistic effect of lipopeptide AC7BS in combination with amphotericin B or fluconazole against C. albicans planktonic cells, biofilm formation and 24 h-old biofilms on medical-grade silicone elastomer disks, in simulated physiological conditions. In co-incubation experiments, AC7BS alone was not effective. However, the combination of AC7BS with the antifungal compounds resulted in a synergistic increase in the efficacy of the drugs against planktonic cells and biofilm, leading to a reduction of MICs and SMICs50. In pre-coating conditions, amphotericin B alone and AC7BS alone significantly inhibited C. albicans biofilms. When the two molecules were tested in association, a synergistic effect was observed on different phases of biofilm formation and a lower SMIC50 was detected. The observed synergism could be related to the combination of the AC7BS anti-adhesive activity and the AMB antifungal effect, but also to the ability of the biosurfactant to affect membranes, thus facilitating AMB entry in the cells. These results suggest that AC7BS can be considered a potential inhibitor of C. albicans biofilm on medical insertional materials and its use as coating agent may potentiate the effect of antifungal compounds such as AMB, when applied in combination

Long-term impact of Global Health educational experiences in Rome. An attempt of measurement

Background Global health education (GHE) is spreading in Europe and in other parts of the world. Since 2008, Sapienza University of Rome has offered activities to medical and other health profession students related to global health (GH), which is grounded in the theory of social determinants of health and inspired by social justice. The educational activities included elective courses as well as community and service-learning experiences, referred to as GH gyms. This study attempts to measure the long-term impact of these educational experiences, especially to demonstrate their influence on the perceived social responsibility of future health professionals. Methods A questionnaire was elaborated and tested on a small sample of participants. It was sent to participants by e-mail. Quantitative results were analysed through descriptive statistics and qualitative answers were carefully read and classified. Results A total of 758 students from different faculties took part to the educational experiences. Only 488 e-mail addresses were available. One hundred and five (21.5%) questionnaires were returned. Participation in GH gyms was perceived to have had a higher influence on future professional and personal choices, when compared to participation in elective GH courses. Conclusions The study shows that consideration of health and social issues related with inequities in health and the use of interactive teaching methodologies had important effects on social responsibility of a large number of students. As there could be a selection bias among respondents, more research is needed to understand the impact of GH educational experiences. The inclusion of global health education in health and social curricula and the use of interactive methodologies with a correct evaluation of results are the indications that emerge from this research, together with the necessity of a strong involvement of students, professors and the whole academic reality

Medical education: an Italian contribution to the discussion on global health education

Abstract Background In Italy an important contribution to the spread of global health education (GHE) grew from the establishment and work of the Italian Network for Global Health Education (INGHE). INGHE gave a national shared definition of global health (GH), grounded in the theory of determinants of health, inspired by a vision of social justice, and committed to reduce health inequities. The aim of this article is to share with the international community INGHE’s point of view on Medical Education. Methods To express its view of medical education at the national level, INGHE established a dedicated commission, which elaborated a first draft of the document and then shared and discussed it with all other members. Results INGHE elaborated a paper where it explained the need to change medical education in order to prepare future health professionals for the challenges of the globalized and unequal world. In this article the authors summarize the experience of INGHE and share with the international community its document. Conclusions The authors believe it is necessary now, more than ever, to insert this new approach to health at social and academic levels. Students should play a fundamental role in the spread of GHE, and activities related with GHE could be considered an important part of the third mission of universities to promote social justice

First-order phase transitions in Yang-Mills theories and the density of state method

When studied at finite temperature, Yang-Mills theories in $3+1$ dimensions display the presence of confinement/deconfinement phase transitions, which are known to be of first order -- the $SU(2)$ gauge theory being the exception. Theoretical as well as phenomenological considerations indicate that it is essential to establish a precise characterisation of these physical systems in proximity of such phase transitions. We present and test a new method to study the critical region of parameter space in non-Abelian quantum field theories on the lattice, based upon the Logarithmic Linear Relaxation (LLR) algorithm. We apply this method to the $SU(3)$ Yang Mills lattice gauge theory, and perform extensive calculations with one fixed choice of lattice size. We identify the critical temperature, and measure interesting physical quantities near the transition. Among them, we determine the free energy of the model in the critical region, exposing for the first time its multi-valued nature with a numerical calculation from first principles, providing this novel evidence in support of a first order phase transition. This study sets the stage for future high precision measurements, by demonstrating the potential of the method.Comment: 25 pages, 21 figures. Version accepted for publicatio

Investigations on ancient beads from the Sultanate of Oman (Ra's al-Hadd - Southern Oman)

A study has been carried out on the mineralogical composition of stone beads found in the course of archaeological excavations carried out at the site of Ra's al-Hadd in Southern Oman. The data provide information about the raw material and technology used for beads production. Several beads and micro-beads made of white paste of different shapes and sizes have been analysed. They range, in size, from two to four millimetres in diameter, two to fifteen millimetres in height, and the diameter of the hole is approximately one millimetre. The shape is tubular for the biggest bead, cylindrical for slender beads and ring-shaped for micro-beads. The beads were analysed using X-ray diffraction (XRD); the method was optimised to minimise the amount of the sample necessary for analysis (15 milligrams were necessary using special sample holders while in traditional holders 300 milligrams are needed). XRD analysis revealed that the beads arc made of “synthetic enstatite”, a magnesium silicate belonging to pyroxene group (orthopy-roxene Mg2Si2O6). The relative intensity of the main peaks confirms that the material is “synthetic enstatite”. Natural enstatite is a hard mineral (its hardness is five or six on the Mohs scale), therefore we propose that a softer magnesium-bearing mineral was used: steatite (Mg5Si4O10 (OH)2 commonly known as massive talc - hardness one on the Mohs scale). The beads might have been worked from soft steatite bulk material and then hardened by transformation of the steatite to synthetic enstatite during firing at about 1000 °C so that the formerly soft beads became hard and durable. Some preliminary heating experiments on talc bulk fired at about 1000 °C was carried out to compare powder diffractograms of the beads and the fired massive talc; a good overall resemblance of the two patterns is evident. The raw material of the examined beads might have came from the ultramafic rocks of Oman and it is very likely that these beads were produced from locally available raw materials.Nous avons étudié la composition minéralogique des petites perles trouvées lors des fouilles archéologiques effectuées sur le site de Ra's al-Hadd situé au sud de l'Oman. Nous avons analysé beaucoup de petites perles et micro-perles fabriquées avec un matériel blanc et de différentes formes et dimensions. Les résultats de l'analyse ont livré des informations sur le matériel et la technologie utilisés pour la production des petites perles. Les dimensions sont de deux à quatre millimètres de diamètre et de deux à quinze millimètres de haut, le diamètre du trou perforé est approximativement de un millimètre. La forme est tubulaire pour la perle la plus grande et cylindrique pour les plus petites perles, de forme circulaire pour les micro-perles. Les petites perles ont été analysées par diffraction de rayons X. Nous avons optimisé la méthode pour minimiser la quantité de matériel utilisé pour l'analyse (15 mg de poudre sont nécessaires avec un porte échantillon spécial contre 500 mg de poudre nécessaires avec un porte échantillon traditionnel). L'analyse par diffraction de rayons X indique que les petites perles sont en enstatite synthétique, un silicate de magnésium appartenant au groupe des pyroxènes (ortopyroxène Mg2Si2O6). L'intensité relative des pics principaux confirme que le matériel utilisé est l'enstatite synthétique. L'enstatite naturelle est un minéral très dur (il a une dureté de cinq à six sur l'échelle Mohs) et c'est pourquoi nous proposons que la stéatite (Mg2Si4O10(OH)2 normalement connue comme talc massif de dureté un sur l'échelle de Mohs) est le matériel utilisé pour la réalisation des petites perles. Les petites perles pourraient avoir été réalisées avec de la stéatite et être ensuite transformées en enstatite synthétique par cuisson au four à une température d'environ 1000 degrés centigrades. Cette méthode permettrait la production de petites perles très dures, réalisées à partir d'un matériel tendre. Nous avons fait des expériences avec du talc italien chauffé à 1000 degrés centigrades pour comparer les diagrammes de diffraction des petites perles avec les diagrammes de diffraction du talc chauffé

Lipoaspirate Shows In Vitro Potential for Wound Healing

Mesenchymal stem cells (MSCs) are a promising therapy in wound healing, although extensive time and manipulation are necessary for their use. In our previous study on cartilage regeneration, we demonstrated that lipoaspirate acts as a natural scaffold for MSCs and gives rise to their spontaneous outgrowth, together with a paracrine effect on resident cells that overcome the limitations connected to MSC use. In this study, we aimed to investigate in vitro whether the microfragmented adipose tissue (lipoaspirate), obtained with Lipogems® technology, could promote and accelerate wound healing. We showed the ability of resident cells to outgrow from the clusters of lipoaspirate encapsulated in a 3D collagen substrate as capability of repopulating a culture of human skin. Moreover, we demonstrated that the in vitro lipoaspirate paracrine effect on fibroblasts and keratinocytes proliferation, migration, and contraction rate is mediated by the release of trophic/reparative proteins. Finally, an analysis of the paracrine antibacterial effect of lipoaspirate proved its ability to secrete antibacterial factors and its ability to modulate their secretion in culture media based on a bacterial stimulus. The results suggest that lipoaspirate may be a promising approach in wound healing showing in vitro regenerative and antibacterial activities that could improve current therapeutic strategies

Endogenous CCL2 neutralization restricts HIV-1 replication in primary human macrophages by inhibiting viral DNA accumulation

Macrophages are key targets of HIV-1 infection. We have previously described that the expressionof CC chemokine ligand 2 (CCL2) increases during monocyte differentiation to macrophages and it is furtherup-modulated by HIV-1 exposure. Moreover, CCL2 acts as an autocrine factor that promotes viral replication ininfected macrophages. In this study, we dissected the molecular mechanisms by which CCL2 neutralization inhibitsHIV-1 replication in monocyte-derived macrophages (MDM), and the potential involvement of the innate restrictionfactors protein sterile alpha motif (SAM) histidine/aspartic acid (HD) domain containing 1 (SAMHD1) and apolipoproteinB mRNA-editing, enzyme-catalytic, polypeptide-like 3 (APOBEC3) family members.Results:CCL2 neutralization potently reduced the number of p24 Gag+cells during the course of either productive orsingle cycle infection with HIV-1. In contrast, CCL2 blocking did not modify entry of HIV-1 based Virus Like Particles, thusdemonstrating that the restriction involves post-entry steps of the viral life cycle. Notably, the accumulation of viralDNA, both total, integrated and 2-LTR circles, was strongly impaired by neutralization of CCL2. Looking for correlates ofHIV-1 DNA accumulation inhibition, we found that the antiviral effect of CCL2 neutralization was independent of themodulation of SAMHD1 expression or function. Conversely, a strong and selective induction of APOBEC3A expression,to levels comparable to those of freshly isolated monocytes, was associated with the inhibition of HIV-1 replicationmediated by CCL2 blocking. Interestingly, the CCL2 neutralization mediated increase of APOBEC3A expression was typeI IFN independent. Moreover, the transcriptome analysis of the effect of CCL2 blocking on global gene expressionrevealed that the neutralization of this chemokine resulted in the upmodulation of additional genes involved in thedefence response to viruses.Conclusions:Neutralization of endogenous CCL2 determines a profound restriction of HIV-1 replication in primaryMDM affecting post-entry steps of the viral life cycle with a mechanism independent of SAMHD1. In addition, CCL2blocking is associated with induction of APOBEC3A expression, thus unravelling a novel mechanism which mightcontribute to regulate the expression of innate intracellular viral antagonistsin vivo. Thus, our study may potentially leadto the development of new therapeutic strategies for enhancing innate cellular defences against HIV-1 and protecting macrophages from infection

Impact of 5-year bottle aging under controlled oxygen exposure on sulfur dioxide and phenolic composition of tannin-rich red wines

Aim: This study aims at understanding the impact of the initial phenolic composition on the evolution of red wines after long bottle aging.Materials and results: three different red wines rich in tannins, Aglianico, Casavecchia and Pallagrello, bottled with the same amount of total sulfur dioxide and different amounts of free sulfur dioxide, were analysed after 5 years of bottle aging under controlled exposure to oxygen passing through the closure. Acetaldehyde and monomeric anthocyanins were determined by HPLC, the chromatic characteristics and the main phenolic classes by spectrophotometry, the saliva precipitation index (SPI) by CHIP electrophoresis, and the astringency subqualities by sensory analysis. The results confirmed that during aging there is an increase in polymerisation reactions. A higher amount of acetaldehyde was detected in wines which were bottled with a lower content of free SO2 and were less rich in anthocyanins and tannins; a significant closure effect was observed for these wines. Regarding the influence of closure on tannins, significant slight differences in vanilline reactive flavans and SPI content were observed for Pallagrello wines only, which were characterised by higher values for tannins at bottling. Astringency subqualities differed with closures for each wine.Conclusion: this study indicates that the amount of initial free and combined sulfur dioxide, as well as that of anthocyanins and tannins, are key factors in driving polymerisation reactions and the aging of red wines. After five years of bottle aging the influence of closure could still be observed.Significance of the study: this study provides new insights into the parameters that need to be evaluated before bottling in order to avoid the wrong evolution of red wines after long bottle aging